Rubradirin and rubradirin B are the most active components of a family of related antibiotics isolated from a strain of streptomyces achromogenes. These compounds contain structural-functional features similar to those found in antibiotics of the ansamycin, movobiocin, and everninomicin class. Rubradirin is a potent inhibitor of Gram-positive bacteria in vitro, and is effective in the systemic treatment of experimental bacterial infections in mice. Rubradirin B is also active against Gram-positive bacteria at low concentrations. Studies pertaining to the mode of action of rubradirin have shown that this antibiotic acts as a potent inhibitor of polypeptide biosynthesis in cell-free systems directed with messenger ribonucleic acid. In addition, the aglycone of rubradirin acts as an extremely potent inhibitor of RNAP. Total syntheses of rubransarol A, rubransarol B and rubaradirin B are presented in this proposal. The synthetic program involves studies on the regiochemistry of the Diels-Alder reaction of unsymmetrically substituted quinones with reactive dienes and the development of general procedures for C-C bond formation by the Lewis acid and transition metal promoted coupling of vinylmetallics and active acid derivatives. This program should be of significant value to the development of more stable analogues of these potent antibiotic systems.